Lyme disease is the most common arthropod-borne infection in the United States. Almost 10,000 cases are reported annually. The spirochete, Borrelia burgdorferi, is the causative agent. In order to examine whether lymphocytes undergo cytopathic changes in response to these spirochetes or products we have undertaken to assess possible interactions between B. burgdorferi and primary or cultured human B- and T-cells in vitro. Although still in preliminary stages, this work has produced strong evidence of two previously unrecognized strategies in bacterial pathogenesis: 1) that Lyme disease spirochetes can specifically target, invade, and kill human lymphocytes, and 2) that the spirochetes may become enveloped in lymphocyte membranes and cytosol, effectively avoiding immune recognition and destruction. These findings are consistent with the view of Lyme disease as an often persistent, low density spirochetosis. Researchers in this group continue to examine these and other characteristics with the ultimate aim of improving the prevention, treatment and diagnosis of Lyme disease.